Prevention of Tryptophan Oxidation During Iodination of Tyrosyl Residues in Peptides

Introduction The conversion of tyrosyl residues into iodo-derivatives can be brought about under different ex­ perimental conditions [1 -3 ] and is essentially an electrophilic substitution by iodine at the phenolic ring of tyrosine. This reaction has been performed for different purposes in protein chemistry, e.g. the iodination of tyrosine has been extensively used in the preparation of labelled proteins and peptidic hor­ mones by using radioactive iodine isotopes [4 -6 ]. U nfortunately this simple and rather popular reac­ tion is not highly selective. Secondary reactions may involve to some extent histidine [7] and sulfur con­ taining amino acids [8 ] yielding side products, which must be eliminated by chromatographic purification of the labelled derivative. A more severe drawback is the oxidative degradation of tryptophan, when pre­ sent, which interfers with a clean iodination of ty­ rosine in peptides. For example, iodination of somatostatin using all available iodinating procedures gave in all cases an heterogeneous family of derivatives each containing an oxidized tryptophan residue [9]. These undesired products can induce erroneous in­ terpretation in receptor studies and radioimmunoas­ says. In this paper we propose the use of Nin-formyl [1 0 ] as tryptophan protecting group during tyrosine iodination.